Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

Amyloidosis and Myeloma Unit Department of Hematology Hospital Clínic of Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Departament od Hematology Transplantology and Internal Medicine Medical University of Warsaw Warsaw Poland

Department of Hemato Oncology University Hospital Olomouc Olomouc Czech Republic

Department of Hematology and Bone Marrow Transplantation St John of Dukla Oncology Center of Lublin Land Lublin Poland

Department of Hematology Blood Neoplasms and Bone Marrow Transplantation Wroclaw Medical University Wroclaw Poland

Department of Hematology Complejo Asistencial de Avila Avila Spain

Department of Hematology Fundeni Clinical Institute University of Medicine and Pharmacy Carol Davila Bucharest Romania

Department of Hematology Hospital del Salvador Santiago Chile

Department of Hematology Medical Faculty University of Warmia and Mazury in Olsztyn Olsztyn Poland

Department of Internal Medicine 2 University Hospital Würzburg Würzburg Germany

Department of Medicine Division of Nephrology Medical College of Wisconsin Milwaukee Wisconsin USA

Department of Nephrology Moscow City Hospital named after S P Botkin Moscow Russian Federation

Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

Division of Hematology Oncology Department of Medicine Medical College of Wisconsin Milwaukee Wisconsin USA

Faculty of Medicine Department of Medicine 1 Medical Center University of Freiburg Freiburg Germany

Federal University of Bahia University Hospital Rede D'or Oncology Sao Paolo Brazil

Hematology Department of Medical Science Surgery and Neuroscience University of Siena Siena Italy

Hematology Unit Department of Onco Hematology Cosenza Italy

Instituto de Investigación Biomédica de Salamanca University Hospital of Salamanca Salamanca Spain

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Nephrology Azienda Ospedaliera Universitaria Senese Siena Italy

Plasma Cell Dyscrasias Center Department of Hematology Jagiellonian University Medical College Faculty of Medicine Cracow Poland

Tel Aviv Medical Center Tel Aviv Israel and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

The John Theurer Cancer Center at Hackensack Meridian School of Medicine Hackensack New Jersey USA

Zobrazit více v PubMed

Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362‐1369. PubMed

Kyle RA, Larson DR, Therneau TM, et al. Long‐term follow‐up of monoclonal Gammopathy of undetermined significance. N Engl J Med. 2018;378(3):241‐249. PubMed PMC

Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538‐e548. PubMed

Mateos MV, Kumar S, Dimopoulos MA, et al. International myeloma working group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020;10(10):102. PubMed PMC

Fermand J‐P, Bridoux F, Dispenzieri A, et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 2018;132(14):1478‐1485. PubMed

Dispenzieri A. Monoclonal gammopathies of clinical significance. Hematology Am Soc Hematol Educ Program. 2020;2020:380‐388. PubMed PMC

Bladé J, Cibeira MT. M‐protein–related disorders: MGCS. Blood. 2018;132:1464‐1465. PubMed

Lomas OC, Mouhieddine TH, Tahri S, Ghobrial IM. Monoclonal Gammopathy of undetermined significance (MGUS)—not so asymptomatic after all. Cancer. 2020;12:1554. PubMed PMC

Merlini G, Stone MJ. Dangerous small B‐cell clones. Blood. 2006;108:2520‐2530. PubMed

Leung N, Bridoux F, Nasr SH. Monoclonal Gammopathy of renal significance. N Engl J Med. 2021;384(20):1931‐1941. PubMed

Leung N, Bridoux F, Hutchison CA, et al. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood. 2012;120(22):4292‐4295. PubMed

Leung N, Bridoux F, Batuman V, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the international kidney and monoclonal Gammopathy research group. Nat Rev Nephrol. 2019;15(1):45‐59. PubMed PMC

Paueksakon P, Revelo MP, Horn RG, Shappell S, Fogo AB. Monoclonal gammopathy: significance and possible causality in renal disease. Am J Kidney Dis. 2003;42(1):87‐95. PubMed

Batko K, Malyszko J, Jurczyszyn A, et al. The clinical implication of monoclonal gammopathies: monoclonal gammopathy of undetermined significance and of renal significance. Nephrol Dial Transplant. 2019;34(9):1440‐1452. PubMed

Sethi S, Rajkumar SV, D'Agati VD. The complexity and heterogeneity of monoclonal immunoglobulin‐associated renal diseases. J Am Soc Nephrol. 2018;29:1810‐1823. PubMed PMC

Steiner N, Göbel G, Suchecki P, Prokop W, Neuwirt H, Gunsilius E. Monoclonal gammopathy of renal significance (MGRS) increases the risk for progression to multiple myeloma: an observational study of 2935 MGUS patients. Oncotarget. 2018;9(2):2344‐2356. PubMed PMC

Fermand J‐P, Bridoux F, Kyle RA, et al. How I treat monoclonal gammopathy of renal significance (MGRS). Blood. 2013;122(22):3583‐3590. PubMed

Kourelis TV, Nasr SH, Dispenzieri A, et al. Outcomes of patients with renal monoclonal immunoglobulin deposition disease. Am J Hematol. 2016;91:1123‐1128. PubMed

Ziogas DC, Kastritis E, Terpos E, et al. Hematologic and renal improvement of monoclonal immunoglobulin deposition disease after treatment with bortezomib‐based regimens. Leuk Lymphoma. 2017;58:1832‐1839. PubMed

Vignon M, Javaugue V, Alexander MP, et al. Current anti‐myeloma therapies in renal manifestations of monoclonal light chain‐associated Fanconi syndrome: a retrospective series of 49 patients. Leukemia. 2017;31:123‐129. PubMed

Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 2019;381:36‐46. PubMed

Lysenko Kozlovskaya LV, Rameev VV, Androsova TV. Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment. Ter Arkh. 2020;92(6):15‐22. PubMed

Bhutani G, Nasr SH, Said SM, et al. Hematologic characteristics of proliferative glomerulonephritides with nonorganized monoclonal immunoglobulin deposits. Mayo Clin Proc. 2015;90(5):587‐596. PubMed

Yadav P, Sathick I, Leung N, et al. Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study. Blood Cancer J. 2020;10:28. PubMed PMC

Nasr SH, Valeri AM, Cornell LD, et al. Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol. 2012;7(2):231‐239. PubMed

Klomjit N, Leung N, Fervenza F, Sethi S, Zand L. Rate and predictors of finding monoclonal gammopathy of renal significance (MGRS) lesions on kidney biopsy in patients with monoclonal gammopathy. J Am Soc Nephrol. 2020;31:2400‐2411. PubMed PMC

Pozzi C, D'Amico M, Fogazzi GB, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis. 2003;42(6):1154‐1163. PubMed

Gozzetti A, Le Beau MM. Fluorescence in situ hybridization: uses and limitations. Semin Hematol. 2000;37:320‐333. PubMed

Kumar S, Paiva B, Anderson KC, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328‐e346. PubMed

Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325‐2332. PubMed

Chauvet S, Frémeaux‐Bacchi V, Petitprez F, et al. Treatment of B‐cell disorder improves renal outcome of patients with monoclonal gammopathy‐associated C3 glomerulopathy. Blood. 2017;129:1437‐1447. PubMed

Cohen C, Royer B, Javaugue V, et al. Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease. Kidney Int. 2015;88:1135‐1143. PubMed

Wechalekar AD, Schonland SO, Kastritis E, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121(17):3420‐3427. PubMed

Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N‐terminal pro‐brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22(18):3751‐3757. PubMed

Lebovic D, Hoffman J, Levine BM, et al. Predictors of survival in patients with systemic Mikhael JR, Schuster SR, Jimenez‐Zepeda VH, et al. cyclophosphamide‐bortezomib‐dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012;119:4391‐4394. PubMed PMC

Abeykoon JP, Zanwar S, Dispenzieri A, et al. Daratumumab‐based therapy in patients with heavily‐pretreated AL amyloidosis. Leukemia. 2019;33:531‐536. PubMed

Bézard M, Oghina S, Vitiello D, et al. Dexamethasone is associated with early deaths in light chain amyloidosis patients with severe cardiac involvement. PLoS ONE. 2021;16(9):e0257189. PubMed PMC

Hogan JJ, Mocanu M, Berns JS. The native kidney biopsy: update and evidence for best practice. Clin J Am Soc Nephrol. 2016;11(2):354‐362. PubMed PMC

Correia SO, Santos S, Malheiro J, Cabrita A, Martins S, Santos J. Monoclonal gammopathy of renal significance: diagnostic workup. World J Nephrol. 2017;6(2):72‐78. PubMed PMC

Telio D, Shepherd J, Forrest D, et al. High‐dose melphalan followed by auto‐SCT has favorable safety and efficacy in selected patients with light chain deposition disease and light and heavy chain deposition disease. Bone Marrow Transplant. 2012;47(3):453‐455. PubMed

Batalini F, Econimo L, Quillen K, et al. High‐dose Melphalan and stem cell transplantation in patients on dialysis due to immunoglobulin light‐chain amyloidosis and monoclonal immunoglobulin deposition disease. Biol Blood Marrow Transplant. 2018;24(1):127‐132. PubMed